SuperAging in HIV-infected Adults: Biopsychosocial Predictors of Neurocognitive Aging Trajectories

项目总结/摘要 接受抗逆转录病毒治疗的艾滋病毒感染者的预期寿命稳步增长。 在美国，估计有50%的PLWH年龄在50岁及以上。尽管寿命延长， ART时代，老年PLWH过早和加速发展老年性 综合征，包括神经认知障碍（NCI），虚弱和日常功能依赖。NeuroHIV 研究优先研究由HIV的神经生物学负担引起的不良后果 然而，三分之一到三分之二的老年人不符合NCI的标准。尽管神经认知 神经认知“未受损”的老年PLWH之间的异质性，神经认知的个体间差异 人们对衰老的轨迹知之甚少。我们最近对一个老年PLWH亚组的特征进行了描述， 年轻的神经认知类似于健康的25岁，在这个年龄，大多数神经认知能力 峰这些被称为超级老年人（SA）的神经认知精英个体显示出类似的HIV特征 与认知正常的非超级和认知受损的同行相比， 有更好的日常功能，精神和身体健康相关的生活质量，更少的合并症， 病前智商这些发现与认知和生理储备模型一致，表明健壮的 认知和生理资源的维持使SA能够有效地对抗神经和身体的 艾滋病毒感染者的压力源然而，这些横截面数据并没有解决SA是否维持 随着时间的推移，最大的神经认知，以及这种神经认知弹性是否与整体 生物心理社会储备指标。评估SA作为反映抗风险能力的结构的有效性 神经认知能力下降对于确定脆弱人群中的神经保护因素至关重要， 老年艾滋病病毒携带者因此，拟议的F31项目旨在1）表征神经认知老化轨迹 并确定其与老年PLWH中SA的关系; 2）确定神经认知功能障碍的生物心理社会预测因子 轨迹; 3）检查人口统计学，神经精神病学，物质使用和日常生活的潜在影响 神经认知轨迹的功能因素。拟议的研究将采用潜在的增长混合物 使用CNS HIV抗逆转录病毒治疗效果中老年PLWH的纵向存档数据建模 研究计划。通过F31机制提供的机会将有助于申请人 专业发展成为一个独立的学术神经心理学家，致力于 促进老年PLWH的神经认知恢复力。

PROJECT SUMMARY/ABSTRACT The life expectancy of people living with HIV (PLWH) receiving antiretroviral therapy (ART) has steadily increased, with an estimated 50% of PLWH in the U.S. aged 50 years and older. Despite increased longevity in the ART-era, older PLWH are at enhanced risk for premature and accelerated development of geriatric syndromes, including neurocognitive impairment (NCI), frailty, and daily functioning dependence. NeuroHIV research preferentially studies adverse outcomes stemming from the combined neurobiological burdens of HIV and aging; however, one to two-thirds of older PLWH do not meet criteria for NCI. Despite the neurocognitive heterogeneity among neurocognitively `unimpaired' older PLWH, inter-individual differences in neurocognitive aging trajectories are poorly understood. We have recently characterized a subgroup of older PLWH with youthful neurocognition akin to that of a healthy 25 year-old, an age at which most neurocognitive capacities peak. These neurocognitively elite individuals, termed SuperAgers (SA), display comparable profiles of HIV disease severity as compared to their cognitively normal non-super and cognitively impaired counterparts, yet have better daily functioning, mental and physical health-related quality of life, fewer comorbidities, and higher premorbid IQ. These findings align with a model of cognitive and physiological reserve, suggesting that robust maintenance of cognitive and physiological resources enables SA to effectively combat the neural and physical stressors of aging with HIV. Nevertheless, these cross-sectional data do not address whether SA maintain maximal neurocognition over time, and whether such neurocognitive resilience converges with holistic indicators of biopsychosocial reserve. Assessing the validity of SA as a construct reflecting resilience against neurocognitive decline is critical toward identifying neuroprotective factors among the vulnerable population of older PLWH. Accordingly, the proposed F31 project aims to 1) characterize neurocognitive aging trajectories and determine their relation to SA in older PLWH; 2) determine biopsychosocial predictors of neurocognitive trajectories; and 3) examine potential effects of demographic, neuropsychiatric, substance use, and daily functioning factors on neurocognitive trajectories. The proposed research will employ latent growth mixture modeling using longitudinal, archival data of older PLWH from the CNS HIV Antiretroviral Therapy Effects Research program. The opportunities afforded via this F31 mechanism will facilitate the applicant's professional development toward becoming an independent academic neuropsychologist dedicated to promoting neurocognitive resilience among older PLWH.